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1.
Br J Neurosurg ; 37(6): 1742-1745, 2023 Dec.
Article in English | MEDLINE | ID: mdl-33645360

ABSTRACT

Large bone defects that occur after resection of calvarial tumours are commonly remedied using titanium meshes or bone prostheses. However, these methods have several problems. While intraoperative extracorporeal radiotherapy for bone flaps could avoid these problems, there have been only a few reports wherein meningiomas were treated with 120 Gy irradiation. Moreover, no reports are available on calvarial metastasis of sarcoma, and the therapeutic radiation dose remains uncertain. Here, we report a case of giant calvarial metastasis of myxoid liposarcoma treated with intraoperative extracorporeal radiotherapy at a dose of 50 Gy. The treatment resulted in successful tumour control followed by favourable bone reconstruction.


Subject(s)
Bone Neoplasms , Plastic Surgery Procedures , Sarcoma , Adult , Humans , Bone Neoplasms/pathology , Bone Neoplasms/radiotherapy , Bone Neoplasms/surgery , Sarcoma/radiotherapy , Sarcoma/surgery , Skull/surgery
2.
Pharmaceuticals (Basel) ; 17(1)2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38275997

ABSTRACT

[64Cu]Cu-diacetyl-bis(N4-methylthiosemicarbazone) ([64Cu]Cu-ATSM) is a radioactive hypoxia-targeting therapeutic agent being investigated in clinical trials for malignant brain tumors. For the quality management of [64Cu]Cu-ATSM, understanding trace metal impurities' effects on the chelate formation of 64Cu and ATSM is important. In this study, we conducted coordination chemistry studies on metal-ATSM complexes. First, the effects of nonradioactive metal ions (Cu2+, Ni2+, Zn2+, and Fe2+) on the formation of [64Cu]Cu-ATSM were evaluated. When the amount of Cu2+ or Ni2+ added was 1.2 mol or 288 mol, equivalent to ATSM, the labeling yield of [64Cu]Cu-ATSM fell below 90%. Little effect was observed even when excess amounts of Zn2+ or Fe2+ were added to the ATSM. Second, these metals were reacted with ATSM, and chelate formation was measured using ultraviolet-visible (UV-Vis) absorption spectra. UV-Vis spectra showed a rapid formation of Cu2+ and the ATSM complex upon mixing. The rate of chelate formation by Ni2+ and ATSM was lower than that by Cu-ATSM. Zn2+ and Fe2+ showed much slower reactions with the ATSM than Ni2+. Trace amounts of Ni2+, Zn2+, and Fe2+ showed little effect on [64Cu]Cu-ATSM' quality, while the concentration of impurity Cu2+ must be controlled. These results can provide process management tools for radiopharmaceuticals.

3.
Brain Nerve ; 70(11): 1301-1305, 2018 Nov.
Article in Japanese | MEDLINE | ID: mdl-30416124

ABSTRACT

Cryptococcosis is a fungal infection that mainly occurs in immunocompromised patients. We present the first case of cryptococcal meningitis in a patient who was being administered everolimus for breast cancer. Everolimus, a selective inhibitor of mammalian target of rapamycin, is a molecular targeting agent that is administered not only as an immunosuppressive agent, but also as an anticancer therapeutic. A 72-year-old woman with recurrent breast cancer had been receiving everolimus. She was admitted to our hospital with headache and vomiting. Lumbar puncture revealed high opening pressure, and cerebrospinal fluid (CSF) evaluation diagnosed cryptococcal meningitis. She was administered liposomal amphotericin-B, followed by fosfluconazole. Daily lumbar puncture was insufficient to reduce the high intracranial pressure; thus, continuous lumbar drainage was needed to improve her symptoms. The indwelling catheter was replaced regularly to prevent bacterial infection. She was treated successfully with extracorporeal CSF drainage for 86 days and fosfluconazole administration over 17 weeks. The patient recovered fully and was discharged on day 153 of hospitalization. As patients who receive everolimus are potentially immunocompromised hosts, we recommend that the medicine be administered with caution considering opportunistic infections when used in patients with cancer. (Received April 19, 2018; Accepted August 9, 2018; Published November 1, 2018).


Subject(s)
Breast Neoplasms/drug therapy , Everolimus/adverse effects , Meningitis, Cryptococcal/diagnosis , Opportunistic Infections/diagnosis , Aged , Everolimus/therapeutic use , Female , Humans , Meningitis, Cryptococcal/therapy , Neoplasm Recurrence, Local , Opportunistic Infections/therapy
4.
No Shinkei Geka ; 46(7): 575-581, 2018 Jul.
Article in Japanese | MEDLINE | ID: mdl-30049898

ABSTRACT

BACKGROUND: Primary central nervous system lymphoma(PCNSL)is a primary brain tumor, which appears commonly and occupies around 4.6% of all primary brain tumors. The standard therapy for this tumor is high-dose methotrexate chemotherapy(HD-MTX)and whole-brain irradiation. No salvage therapies for HD-MTX therapy-refractory or recurrent PCNSLs have been standardized. In our institution, ESHAP therapy(high-dose cytarabine:2,000mg, cisplatin:25mg/m2, etoposide:40mg/m2, methylprednisolone:500mg)was administered as a secondary chemotherapy, and the efficiency was examined. METHODS: We administered ESHAP therapy as secondary chemotherapy for patients with refractory/recurrent PCNSL after HD-MTX therapy. Patients with PCNSL who were diagnosed and treated at our institute since 1996 were retrospectively studied. Clinical evaluations were performed based on Karnofsky Performance Status and overall survival, and the effect of ESHAP therapy was evaluated using the Response Assessment in Neuro-Oncology criteria. RESULTS: The number of patients with refractory/recurrent PCNSLs were 18(28-77 years of age, median age of 58.5 years). The response rate(RR)after the first course of salvage ESHAP therapy was 77.8%(14 cases), and complete response(CR)was achieved in 6 cases. The RR after the final course of ESHAP therapy was as high as 61.1%(11 cases), and 4 patients retained CR status. In patients with refractory PCNSL who were treated with HD-MTX, the RR in the final course of salvage ESHAP therapy was as high as 77.8%(7 cases), and 3 patients retained CR status during the periods. The occurrence rate of Grade 3 or higher adverse events, according to the Common Terminology Criteria for Adverse Events version 4.0, was 66.7%(12 cases);all events that were associated with blood and lymphatic system disorders were quickly alleviated, and no fatal adverse events occurred. CONCLUSION: In this study, we retrospectively examined the efficacy of ESHAP therapy as a secondary chemotherapy for patients with refractory/recurrent PCNSL after receiving HD-MTX therapy. Based on our findings, we suggest that ESHAP therapy should be considered as an encouraging secondary chemotherapy for patients with refractory/recurrent PCNSL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Central Nervous System Neoplasms , Cisplatin , Cytarabine , Lymphoma , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Cisplatin/administration & dosage , Cytarabine/administration & dosage , Etoposide/administration & dosage , Humans , Lymphoma/drug therapy , Methylprednisolone/administration & dosage , Middle Aged , Retrospective Studies
5.
Int J Oncol ; 47(1): 61-70, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25963555

ABSTRACT

Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called 'cancer xenopatients') are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lympho-proliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.


Subject(s)
Neoplasm Transplantation/methods , Neoplasms/pathology , Transplantation, Heterologous/methods , Adult , Aged , Aged, 80 and over , Animals , Disease Models, Animal , Female , Humans , Male , Mice , Middle Aged , Precision Medicine , Xenograft Model Antitumor Assays , Young Adult
6.
Int J Oncol ; 42(3): 881-6, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23338840

ABSTRACT

The signal transducer and activator of transcription 3 (STAT3) factor plays an important role in the tumorigenicity of cancer stem cells. The purpose of this study was to investigate the inhibitory mechanism of this pathway acting through the tumor suppressor von Hippel-Lindau (VHL) protein in glioma cancer stem cells. We isolated floating neurosphere-forming CD133+ cells as glioma stem-like cells (GSLCs) by the MACS method. Furthermore, we examined these cells for their growth rate, ability to form colonies and neurospheres in soft agar, capacity for implantation into SCID mice and expression of CD133, STAT3, JAK2, Elongin A, PTEN and VHL. Furthermore, we transferred the VHL gene, an inhibitor of STAT3, into GSLCs using an adenovirus vector and compared these transfectants with control vector-transfected GSLCs. GSLCs proved to be implantable and formed a tumor in the subcutaneous tissue of SCID mice, the histology of which was similar to that of human glioblastomas. In addition, GSLCs exhibited a high capacity for soft agar colony and neurosphere formation, nearly all of which were CD133 positive. The majority of GSLCs were immunopositive for STAT3, JAK2 and Elongin A, but immunonegative for PTEN and VHL. When the VHL gene was transferred to GSLCs and these cells were transplanted into SCID mice, they did not result in tumor formation. Their capacity for soft agar colony and neurosphere formation was significantly inhibited, although their proliferation was only moderately inhibited. Regarding the expression of various factors, that of CD133 was decreased in the VHL transfectants and those of STAT3, JAK2 and Elongin A were eliminated. However, the expression of PTEN and of VHL was upregulated. These findings suggest that VHL regulated the tumorigenicity and self-renewal ability of glioma cancer stem cells by inhibiting the JAK/STAT signaling pathway.


Subject(s)
Glioma/metabolism , Janus Kinases/antagonists & inhibitors , Neoplastic Stem Cells/metabolism , STAT3 Transcription Factor/antagonists & inhibitors , Von Hippel-Lindau Tumor Suppressor Protein/metabolism , AC133 Antigen , Animals , Antigens, CD/biosynthesis , Cell Line, Tumor , Cell Proliferation , Cell Transformation, Neoplastic , Elongin , Gene Transfer Techniques , Glioma/genetics , Glycoproteins/biosynthesis , Humans , Janus Kinase 2/biosynthesis , Janus Kinases/metabolism , Mice , Mice, SCID , Neoplasm Transplantation , PTEN Phosphohydrolase/biosynthesis , Peptides , STAT3 Transcription Factor/biosynthesis , STAT3 Transcription Factor/metabolism , Signal Transduction/genetics , Transcription Factors/biosynthesis , Transplantation, Heterologous , Von Hippel-Lindau Tumor Suppressor Protein/biosynthesis , Von Hippel-Lindau Tumor Suppressor Protein/genetics
7.
Int J Clin Oncol ; 12(2): 125-30, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17443280

ABSTRACT

BACKGROUND: The efficacy of individual chemotherapy based on chemosensitivity has scarcely been studied. METHODS: We examined the chemosensitivites for four anticancer agents - 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3 (2-chloroethyl)-3-nitrosourea hydrochloride (ACNU), carboplatin, cisplatin, and etoposide - of 43 malignant astrocytic tumors (21 anaplastic astrocytomas and 22 glioblastomas) by using a collagen gel matrix assay, and we also determined the survival periods of the tumor-bearing patients. The chemosensitivity was evaluated in terms of the growth inhibition rate, using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) method. RESULTS: For the anaplastic astrocytomas, the mean growth inhibitory rate was 33.2% with cisplatin, 37.2% with carboplatin, 28.0% with ACNU, and 24.8% with etoposide. For the glioblastomas, these rates were 36.9%, 42.3%, 23.2%, and 34.8%, respectively. The median overall and progression-free survivals of anaplastic astrocytoma-bearing patients who had undergone chemotherapy with two anticancer drugs, both of which showed significant anticancer activity (growth inhibitory rate >30%) were significantly longer than those of the patients who had been treated with two drugs, one or both of which did not show significant anticancer activity. On the other hand, there was no significant difference in the overall or the progression-free survivals in the two corresponding groups of glioblastoma-bearing patients. CONCLUSION: The collagen gel matrix assay is clinically useful to determine in vitro chemosensitivity that reflects in vivo chemosensitivity. Individual chemotherapy for malignant astrocytic tumors, based on chemosensitivity data, could contribute to longer survival, particularly in anaplastic astrocytoma-bearing patients.


Subject(s)
Antineoplastic Agents/therapeutic use , Astrocytoma/drug therapy , Astrocytoma/pathology , Carboplatin/therapeutic use , Cisplatin/therapeutic use , Collagen , Etoposide/therapeutic use , Nimustine/therapeutic use , Adult , Aged , Central Nervous System Neoplasms/drug therapy , Disease Progression , Disease-Free Survival , Drug Screening Assays, Antitumor , Female , Fibrin Foam , Follow-Up Studies , Glioblastoma/drug therapy , Glioblastoma/pathology , Humans , Japan , Karnofsky Performance Status , Male , Middle Aged , Sensitivity and Specificity , Survival Analysis , Tissue Adhesives , Treatment Outcome , Tumor Burden/drug effects , Tumor Cells, Cultured/drug effects
8.
Cancer Res ; 66(11): 5883-91, 2006 Jun 01.
Article in English | MEDLINE | ID: mdl-16740728

ABSTRACT

Restricted and high-level expression of interleukin-13 receptor alpha2 (IL-13Ralpha2) in a majority of human malignant gliomas makes this protein an attractive vaccine target. We have previously described the identification of the IL-13Ralpha2(345-353) peptide as a human leukocyte antigen-A2 (HLA-A2)-restricted CTL epitope. However, as it remains unclear how efficiently peptide-based vaccines can induce specific CTLs in patients with malignant gliomas, we have examined whether analogue epitopes could elicit heteroclitic antitumor T-cell responses versus wild-type peptides. We have created three IL-13Ralpha2 analogue peptides by substitutions of the COOH-terminal isoleucine (I) for valine (V) and the NH(2)-terminal tryptophan (W) for either alanine (A), glutamic acid (E), or nonsubstituted (W; designated as 1A9V, 1E9V, and 9V, respectively). In comparison with the native IL-13Ralpha2 epitope, the analogue peptides 9V and 1A9V displayed higher levels of binding affinity and stability in HLA-A2 complexes and yielded an improved stimulatory index for patient-derived, specific CTLs against the native epitope expressed by HLA-A2(+) glioma cells. In HLA-A2-transgenic HHD mice, immunization with the peptides 9V and 1A9V induced enhanced levels of CTL reactivity and protective immunity against an intracranial challenge with IL13Ralpha2-expressing syngeneic tumors when compared with vaccines containing the native IL-13Ralpha2 epitope. These findings indicate highly immunogenic IL-13Ralpha2 peptide analogues may be useful for the development of vaccines capable of effectively expanding IL-13Ralpha2-specific, tumor-reactive CTLs in glioma patients.


Subject(s)
Cancer Vaccines/immunology , Glioma/immunology , Glioma/therapy , Peptide Fragments/immunology , Receptors, Interleukin/immunology , T-Lymphocytes, Cytotoxic/immunology , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/pharmacology , Cell Line, Tumor , HLA-A2 Antigen/immunology , Humans , Interleukin-13 Receptor alpha1 Subunit , Lymphocyte Activation/drug effects , Mice , Mice, Transgenic , Peptide Fragments/pharmacology , Receptors, Interleukin-13 , T-Lymphocytes, Cytotoxic/drug effects
9.
Auris Nasus Larynx ; 33(1): 67-70, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16168589

ABSTRACT

We describe a case of small cell carcinoma arising in the nasal cavity using combined chemotherapy with irinotecan (CPT-11)/cisplatin followed by surgical salvage which successfully avoided a radical operation. In a follow-up no local recurrence was observed over 3 years after the operation. Ours is the first report of the use of combined irinotecan (CPT-11)/cisplatin chemotherapy in small cell carcinoma of the nasal cavity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Nasal Cavity/pathology , Nose Neoplasms/drug therapy , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Carcinoma, Small Cell/surgery , Cisplatin/administration & dosage , Female , Humans , Irinotecan , Nasal Cavity/surgery , Neoadjuvant Therapy , Nose Neoplasms/surgery
10.
J Immunol ; 175(4): 2730-40, 2005 Aug 15.
Article in English | MEDLINE | ID: mdl-16081851

ABSTRACT

We tested whether modulation of the CNS-tumor microenvironment by delivery of IFN-alpha-transduced dendritic cells (DCs: DC-IFN-alpha) would enhance the therapeutic efficacy of peripheral vaccinations with cytokine-gene transduced tumor cells. Mice bearing intracranial GL261 glioma or MCA205 sarcoma received peripheral immunizations with corresponding irradiated tumor cells engineered to express IL-4 or GM-CSFs, respectively, as well as intratumoral delivery of DC-IFN-alpha. This regimen prolonged survival of the animals and induced tumor-specific CTLs that expressed TRAIL, which in concert with perforin and Fas ligand (FasL) was involved in the tumor-specific CTL activity of these cells. The in vivo antitumor activity associated with this approach was abrogated by administration of neutralizing mAbs against TRAIL or FasL and was not observed in perforin-/-, IFN-gamma-/-, or FasL-/- mice. Transduction of the tumor cells with antiapoptotic protein cellular FLIP rendered the gene-modified cells resistant to TRAIL- or FasL-mediated apoptosis and to CTL killing activity in vitro. Furthermore, the combination therapeutic regimen was ineffective in an intracranial cellular FLIP-transduced MCA205 brain tumor model. These results suggest that the combination of intratumoral delivery of DC-IFN-alpha and peripheral immunization with cytokine-gene transduced tumor cells may be an effective therapy for brain tumors that are sensitive to apoptotic signaling pathways.


Subject(s)
Apoptosis/immunology , Brain Neoplasms/immunology , Cancer Vaccines/immunology , Dendritic Cells/metabolism , Dendritic Cells/transplantation , Glioma/immunology , Interferon-alpha/administration & dosage , Signal Transduction/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/genetics , Adoptive Transfer , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Brain Neoplasms/pathology , Brain Neoplasms/prevention & control , Cancer Vaccines/administration & dosage , Cancer Vaccines/genetics , Cell Line, Tumor , Cytokines/biosynthesis , Cytokines/physiology , Cytokines/therapeutic use , Cytotoxicity, Immunologic , Dendritic Cells/immunology , Glioma/pathology , Glioma/prevention & control , Injections, Intralesional , Injections, Intraventricular , Interferon-alpha/genetics , Interferon-alpha/metabolism , Lymph Nodes/immunology , Lymph Nodes/pathology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Knockout , Transduction, Genetic
11.
Cancer Gene Ther ; 12(9): 757-68, 2005 Sep.
Article in English | MEDLINE | ID: mdl-15832173

ABSTRACT

We have created a novel cellular vehicle for gene therapy of malignant gliomas by transfection of murine bone marrow stroma cells (MSCs) with a cDNA encoding epidermal growth factor receptor (EGFR). These cells (EGFR-MSCs) demonstrate enhanced migratory responses toward glioma-conditioned media in comparison to primary MSCs in vitro. Enhanced migration of EGFR-MSC was at least partially dependent on EGF-EGFR, PI3-, MAP kinase kinase, and MAP kinases, protein kinase C, and actin polymerization. Unlike primary MSCs, EGFR-MSCs were resistant to FasL-mediated cytotoxicity and were capable of stimulating allogeneic mixed lymphocyte reaction, suggesting EGFR-MSCs possess suitable characteristics as vehicles for brain tumor immuno-gene therapy. Following injection at various sites, including the contralateral hemisphere in the brain of syngeneic mice, EGFR-MSCs were able to migrate toward GL261 gliomas or B16 melanoma in vivo. Finally, intratumoral injection with EGFR-MSC adenovirally engineered to secrete interferon-alpha to intracranial GL261 resulted in significantly prolonged survival in comparison to controls. These data indicate that EGFR-MSCs may serve as attractive vehicles for infiltrating brain malignancies such as malignant gliomas.


Subject(s)
Bone Marrow Cells/physiology , Brain Neoplasms/therapy , Cell Movement , ErbB Receptors/genetics , Genetic Therapy/methods , Glioma/therapy , Actins/metabolism , Animals , Bone Marrow Cells/cytology , Cell Line , Epidermal Growth Factor/metabolism , Mice , Phosphatidylinositol 3-Kinases/metabolism , Protein Kinase C/metabolism , Stromal Cells/physiology , Transfection
12.
J Neurosurg ; 102(2): 295-301, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15739558

ABSTRACT

OBJECT: The goal of this study was to evaluate intraoperative power Doppler ultrasonography when used with a contrast-enhancing agent for operations on intracranial tumors. METHODS: Forty intracranial tumors were examined using power Doppler ultrasonography with a galactose microparticle-based ultrasonographic contrast-enhancing agent during operations on the brain. The tumors included 37 intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and three nonneoplastic lesions). All patients also underwent computerized tomography and magnetic resonance imaging, and all but three of the patients underwent digital subtraction (DS) angiography. Before injection of the ultrasonographic contrast agent, intra- and peritumoral power Doppler flow signals were detected in 32 of the intracranial tumors. After the injection, the signals were enhanced in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 +/- 69 seconds) after the injection. Among the tumors, hemangioblastomas displayed particularly strong contrast enhancement. In these intracranial tumors, the echo signals obtained using contrast-enhanced power Doppler ultrasonography correlated with DS angiographic staining. Power Doppler ultrasonograms with the appropriate contrast agent provided better data on the precise real-time position of the tumors and their relationship to adjacent vessels than ultrasonograms obtained before the injection of the contrast agent. CONCLUSIONS: Intraoperative power Doppler ultrasonography performed using a contrast-enhancing agent can facilitate intraoperative real-time navigation and assessment of the intratumoral vasculature and peritumoral vessels, particularly for tumors having abundant vessels such as hemangioblastomas.


Subject(s)
Brain Neoplasms/diagnostic imaging , Contrast Media/administration & dosage , Glioma/diagnostic imaging , Image Enhancement , Image Processing, Computer-Assisted , Polysaccharides , Ultrasonography, Doppler, Transcranial , Adolescent , Adult , Aged , Analysis of Variance , Angiography, Digital Subtraction , Brain/pathology , Brain/surgery , Brain Neoplasms/blood supply , Brain Neoplasms/secondary , Brain Neoplasms/surgery , Cerebral Angiography , Child , Child, Preschool , Female , Glioma/blood supply , Glioma/pathology , Glioma/surgery , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neovascularization, Pathologic/diagnostic imaging , Neovascularization, Pathologic/pathology , Neovascularization, Pathologic/surgery , Neuronavigation , Sensitivity and Specificity , Tomography, X-Ray Computed
13.
Cancer Res ; 64(16): 5830-8, 2004 Aug 15.
Article in English | MEDLINE | ID: mdl-15313927

ABSTRACT

We evaluated the effects, on immunity and survival, of injection of interferon (IFN)-alpha-transfected dendritic cells (DC-IFN-alpha) into intracranial tumors in mice immunized previously with syngeneic dendritic cells (DCs) pulsed either with ovalbumin-derived CTL or T helper epitopes. These immunizations protected animals from s.c. challenge with ovalbumin-expressing M05 melanoma (class I+ and class II-negative). Notably, antiovalbumin CTL responses were observed in animals vaccinated with an ovalbumin-derived T helper epitope but only after the mice were challenged with M05 cells. This cross-priming of CTL was dependent on both CD4+ and CD8+ T cells. Because we observed that s.c., but not intracranial, tumors were infiltrated with CD11c+ DCs, and because IFN-alpha promotes the activation and survival of both DCs and T cells, we evaluated the combinational antitumor effects of injecting adenoviral (Ad)-IFN-alpha-engineered DCs into intracranial M05 tumors in preimmunized mice. Delivery of DC-IFN-alpha prolonged survival. This was most notable for animals prevaccinated with both the CTL and T helper ovalbumin epitopes, with 60% (6 of 10) of mice (versus 0 of 10 of control animals) surviving for > 80 days after tumor challenge. DC-IFN-alpha appeared to persist longer than mock-transfected DCs within the intracranial tumor microenvironment, and DC-IFN-alpha-treated mice exhibited enhanced levels of ovalbumin-specific CTL in draining cervical lymph nodes. On the basis of these results, we believe that local expression of IFN-alpha by DCs within the intracranial tumor site may enhance the clinical efficacy of peripheral vaccine approaches for brain tumors.


Subject(s)
Brain Neoplasms/therapy , Cancer Vaccines/immunology , Cancer Vaccines/pharmacology , Dendritic Cells/immunology , Immunotherapy, Adoptive/methods , Interferon-alpha/immunology , Amino Acid Sequence , Animals , Brain Neoplasms/immunology , Brain Neoplasms/prevention & control , Epitopes, T-Lymphocyte/immunology , Female , Interferon-alpha/genetics , Melanoma, Experimental/immunology , Melanoma, Experimental/prevention & control , Melanoma, Experimental/therapy , Mice , Mice, Inbred C57BL , Molecular Sequence Data , Ovalbumin/immunology , Ovalbumin/pharmacology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Helper-Inducer/immunology , Transfection
15.
Am J Otolaryngol ; 25(1): 68-72, 2004.
Article in English | MEDLINE | ID: mdl-15011209

ABSTRACT

We present a rare case of bilateral cerebrospinal fluid (CSF) otorrhea via multiple bony defects in the left tegmen and a single defect with the herniated brain tissue on the right side. Initially, the patient complained of left hearing loss and fullness and was diagnosed with serous otitis media. After myringotomy, the pulsating watery discharge suggested CSF otorrhea. Five months after surgical repair of the left side, right-side CSF leakage occurred. The right side was repaired surgically, and the patient recovered without incident. From our findings and a review of the literature, we postulate that bilateral CSF otorrhea resulted mainly from the thinness of the tegmen because of well-pneumatized mastoid air cells and the weakness of the dura after chronic inflammatory changes. In case of spontaneous CSF otorrhea, the roof of tegmen should be assessed bilaterally with care using radiologic examinations so as not to overlook a subclinical condition on the contralateral side.


Subject(s)
Cerebrospinal Fluid Otorrhea/etiology , Cerebrospinal Fluid Otorrhea/diagnosis , Cerebrospinal Fluid Otorrhea/surgery , Diagnosis, Differential , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Tomography, X-Ray Computed
17.
Otol Neurotol ; 23(6): 832-5, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12438841

ABSTRACT

OBJECTIVES: To evaluate the clinical features of labyrinthine fistulae occurring as a late complication of middle ear surgery using the canal wall down technique. STUDY DESIGN: This was a retrospective study of the past 23 years, conducted at a single tertiary care center. The authors evaluated the backgrounds, clinical features, and surgical findings in 25 patients with labyrinthine fistulae, who had a history of ear surgery using the canal down technique and who underwent a second operation at their hospital. INTERVENTIONS: All the patients underwent revision surgery because of persistent or recurrent vertigo caused by labyrinthine fistulae, circumscribed labyrinthitis, or suppurative labyrinthitis. MAIN OUTCOME MEASURES: The clinical features of this disease entity were assessed by history, surgical findings, and the results of audiovestibular testing. RESULTS: The patients had a long history of repetitive postoperative aural discharge before experiencing vertigo, which initially occurred 4 to 64 years (average, 20.2 years) after the previous operation. At the first visit to the authors' clinic, the results of a fistula test conducted with a Politzer's bulb were positive in 14 patients and negative in 5 patients. In the remaining 6 ears, pressure loading of the ear canal induced the sensation of vertigo without accompanying nystagmus. Surgical intervention showed that the fistulae were located at the lateral semicircular canal in 19 ears, at the footplate of the stapes in 4 ears, and at the promontory in 2 ears. Labyrinthine fistulae were closed with conchal cartilage, bone paste (bone dust mixed with fibrin glue), and/or temporalis fascia. In some patients, the fistulae were further covered with pedicled temporalis muscle. In 2 cases complicated by acute suppurative labyrinthitis, the mastoid cavity was obliterated after completion of the labyrinthectomy. The postoperative courses in all patients were uneventful. CONCLUSIONS: A labyrinthine fistula may be created by repeated and insidious infection of a mastoid cavity that has been exposed to the outside during canal wall down surgery. Intensive care of the opened mastoid cavity is essential to avoid this late complication.


Subject(s)
Cholesteatoma, Middle Ear/surgery , Fistula/surgery , Labyrinth Diseases/surgery , Labyrinthitis/surgery , Otitis Media/surgery , Postoperative Complications/surgery , Adolescent , Adult , Aged , Child , Child, Preschool , Chronic Disease , Ear Canal/surgery , Female , Fistula/diagnosis , Humans , Labyrinth Diseases/diagnosis , Labyrinthitis/diagnosis , Male , Meniere Disease/diagnosis , Meniere Disease/surgery , Middle Aged , Postoperative Complications/diagnosis , Reoperation , Retrospective Studies
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